Monday, November 15, 2004

Fruits of Bias: By now, everyone's heard of the wonderful new drug combination that will save the lives of many people of African descent:

A two-drug combination pill dramatically reduced deaths among blacks with heart failure, a landmark finding that is expected to lead to government approval of the first medication marketed for a specific race.

Black cardiologists hailed this form of racial profiling after years in which minorities got short shrift in medical studies. Others complained that the drug also might help whites and should have been tested in them, but wasn't for business reasons.

'At times you can't win,' said Dr. Augustus Grant, past president of the Association of Black Cardiologists, which supported the study. 'Here we have a wonderful trial that shows a clear result and the issue is raised, 'Why was this trial only done in African Americans?''

Good question. If what you were really looking for is a drug that would work better in blacks than in whites, wouldn't you compare the impact of the drug on the two groups? Why, yes, you would. But that's not what the researchers did. Perhaps it was because the researchers know there's a great demand and interest in research that's conducted on people of African descent, and focusing their research on that population is more likely to result in publication. Perhaps it was because the researchers who conducted the study have a genuine interest in only studying people of African descent. Or, perhaps it's because one of the researchers holds two patents on the drug combination used in the study and he had a vested interest in making the combination look good. Or, perhaps it was because the company sponsoring the study, NitroMed, has applied for a patent that specifies the drug for use specifically in patients of African descent. Either way, there's an obvious inherent bias in the study.

And by the way, the results weren't all that impressive. Certainly not "dramatic." The study followed patients for an average of ten months. Of those who took the drug combination, 6.2% died by the end of the trial compared to 10.2% of those who took placebo, for a difference of 4 percentage points. The two groups also differed in the incidence of heart failure exacerbations by about four percentage points. But the incidence of side effects was much higher in the treatment group - 47.5% experienced headaches, compared to 19.2% in the placebo group; 29.3% experienced dizziness compared to 12.3% in the placebo group. You've got to wonder if it's really worth taking.

The idea of finding drugs that work best within a genetic make-up is a good one. An one day, when the science of genomic medicine is better developed, we may be able to choose drugs that will work best for an individual genetic make-up. But this study is no nowhere near that level. And it bears all the marks of spinning the data to fit the researchers - and their sponsors's -best interests, rather than those of patients.

UPDATE: A reader takes me to task:

I agree with the thrust of your comment that we need to watch out for vested interests in designing studies, etc., and in this case, there is an extra angle associated with race. But I think that you have the details of this particular story a bit wrong, despite the fact that you are generally right about such things. I speak particularly of your comment to this effect:

"perhaps it's because one of the researchers holds two patents on the drug combination used in the study and he had a vested interest in making the combination look good."

Now, I occasionally have reason to do things professionally with Jay Cohn, the cardiologist here at U Minnesota whose brainchild is the therapeutic combination of hydralazine and isosorbide compounds.... I don't see where that says anything about his motives for this project.

I would bet my wife and daughters- well, not them, but you get the idea- that his presence on patent 6,784,177 has exactly zero to do with conflicts of interest to get big dollars from the combination drug. For starters, he doesn't need the money- if he was driven by cash, he would not still be in academia as a very well-known practitioner with a CV 8 miles long, he would be in big deal practice out there working for famous and rich CHF patients like Richard DeVos.

Cohn has been crusading for 20 years to find anyone who will test the two drugs together to get the therapy qualified for on-label scripts, but no one had any interest because the compounds themselves were/are generic and out of patent coverage. The patent itself is a method patent- meaning that it is essentially unenforceable; anyone who reads the clinical studies can just go use the therapy with no one paying any attention at all. The only
reason to patent the thing at all is PR for the company that finally took up the cause. Cohn frankly admits that he is in the African-American application solely because it was the only way he could get this tested at all. Anyone who challenged the claims of that patent or was challenged by an enforcement attempt would have it killed so fast your head would spin. In the real world, the patent is about as financially useful as Bayer patenting the idea of women over 50 taking 80mg a day of aspirin to reduce the possibility of MI. Cohn frankly tells anyone that he wants nothing more than for everyone to prescribe those drugs together in appropriate dosages for HF, wherever they get them. If the company makes some money on a convenient single pill, fine.

And I find the motives of those decrying the study on "ethical" grounds pretty suspect; the Jonathan Kahns of the world are more concerned that African Americans will start to see health care redlining or the rebirth of the old IQ controversy as part of the eugenics debate than they are about treating patients.